Changes in Inflammatory Biomarkers Across Weight Classes in a ...

J Gastrointest Surg (2009) 13:1205–1212 DOI 10.1007/s11605-009-0904-9

2008 SSAT POSTER PRESENTATION

Changes in Inflammatory Biomarkers Across Weight Classes in a Representative US Population: A Link Between Obesity and Inflammation Xuan-Mai T. Nguyen & John Lane & Brian R. Smith & Ninh T. Nguyen

Received: 31 December 2008 / Accepted: 15 April 2009 / Published online: 5 May 2009 # The Author(s) 2009. This article is published with open access at Springerlink.com

Abstract Background Obesity has been linked with a chronic state of inflammation which may be involved in the development of metabolic syndrome, cardiovascular disease, non-alcoholic steatohepatitis, and even cancer. The objective of this study was to examine the association between obesity class and levels of inflammatory biomarkers from men and women who participated in the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Methods Serum concentrations of C-reactive protein (CRP) and fibrinogen were measured among US participants of the 1999–2004 NHANES. We examined biomarker levels across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as BMI of 30 kg/m2) and two-thirds being overweight.1 Health conditions associated with excess weight include increased risk for type II diabetes, hypertension, dyslipidemia, metabolic syndrome, atherosclerosis, degenerative joint disorders, obstructive sleep apnea, and certain cancers.2–8 Obesity is also associated with cardiovascular disease which is the leading cause of mortality in the United States.9 While the mechanistic relationship between obesity and the development of obesity-related conditions are not clearly understood, there is growing evidence to support the role of inflammation as a possible link.10–13 C-reactive protein (CRP) and fibrinogen are biomarkers representing increased risk for cardiovascular morbidity and mortality.14,15 CRP, the most extensively studied inflam-

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matory biomarker, is a protein produced by hepatocytes in the presence of inflammation due to factors such as infection, injury, or conditions such as obesity.16 Elevated levels of CRP have been associated with increased inflammation in the coronary arteries, and thus a marker for increased risk for atherosclerosis and cardiovascular disease.17,18 A meta-analysis of seven studies comparing individuals within the top third with those within the bottom third at study baseline showed that higher CRP levels were associated with a risk ratio of 1.7 (95% CI 1.4– 2.1) for coronary heart disease (CHD).19 Additionally, studies using older NHANES III (1988–1994) data have shown that levels of CRP are elevated in individuals with high BMI.20,21 Another inflammatory biomarker that plays a direct role in coronary artery thrombosis is fibrinogen.22 Fibrinogen, a major coagulation protein and the precursor to fibrin, is a major determinant of platelet aggregation and plasma viscosity.23,24 To our knowledge, no studies to date have examined the relationship between fibrinogen levels and body weight, but a meta-analysis of 18 studies examining the association between fibrinogen and CHD found that individuals with fibrinogen values within the top third compared to individuals within the bottom third of the study distribution had a high risk ratio of 1.8 (95% CI 1.6– 2.0) for development of CHD.18 Since the relationship between obesity and cardiovascular disease, as well as the relationship between inflammation and cardiovascular disease, had been established, this study aimed to examine the association between obesity class and levels of inflammatory biomarkers (CRP and fibrinogen) utilizing more recent data from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. We hypothesized that there is a direct relationship between the levels of inflammatory biomarkers with increasing degree of obesity and there is an interaction between level of biomarkers and diabetes and hypertension.

J Gastrointest Surg (2009) 13:1205–1212

subjects signed a consent form approved by the Human Subjects Committee in the US Department of Health and Human Services. 25–27 The three latest, continuous NHANES dataset were collected between 1999–2000, 2001–2002, and 2003–2004. Prior to 1999, the NHANES were performed in cluster as NHES I (1960–1962), NHANES I (1971–1974), NHANES II (1976–1980), and NHANES III (1988–1994). Additional information from each participant was collected during an in-home interview and subsequent medical evaluation at a mobile examination center. During the in-home interview, information on age (limited to participants ≥20 years), sex, race/ethnicity, smoking history, alcohol consumption, history of diabetes mellitus, history of arthritis, and medication usage was obtained. Participants currently smoking a cigarette, pipe and/or cigar were classified as smokers while alcohol consumption was defined as having at least one drink per week in the past 12 months. The prevalence of arthritis was self-reported and defined as ever being told by a doctor or health professional. At the mobile examination center, blood pressure measurements were taken by trained interviewers and physicians using standardized measurement protocols recommended by the American Heart Association.28 Height, weight, and lipid profile measurements were determined using standard protocols. More details are provided in the NHANES Laboratory/Medical Technologists Procedures Manual.29 Participants were considered to have hypertension if their mean systolic blood pressure, measured at the mobile examination center, was greater than 140 mmHg or mean diastolic blood pressure was greater than 90 mmHg, if they were told by their doctor that they have high blood pressure or hypertension, or if they were taking antihypertensive medications. Diabetes mellitus was self-reported and defined to include subjects who were told by their doctor they have diabetes and subjects who stated that they were currently using antidiabetic medication(s) such as insulin or oral hypoglycemic agents.

Subjects and Methods Definition of Obesity Study Population The NHANES is conducted by the National Center for Health Statistics which is part of the Centers for Disease Control and Prevention. The NHANES provides crosssectional health and nutrition data for the US population. The survey examines a nationally representative complex, multistage probability sample of about 5,000 US civilians each year, located within 15 counties across the country. The NHANES survey consists of an extensive health information interview, a complete physical examination, and extensive laboratory testing. The physical examinations were performed in a mobile examination center and all

Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. The National Heart, Lung, and Blood Institute’s definition for overweight and obesity were used to categorize the degree of obesity. A BMI